Letter | Published:

Multiple essential functions of neuregulin in development

Nature volume 378, pages 386390 (23 November 1995) | Download Citation

Subjects

Abstract

NEUREGULIN (also called NDF, heregulin, GGF and ARIA) is a member of the EGF family which induces growth and differentiation of epithelial, glial and muscle cells in culture1–4. The biological effects of the factor are mediated by tyrosine kinase receptors. Neuregulin can bind directly to erbB3 and erbB4 and receptor heterodimerization allows neuregulin-dependent activation of erbB2 (refs 1, 2, 5). A targeted mutation in mice reveals multiple essential roles of neuregulin in development. Here we show that neuregulin -/ - embryos die during embryogenesis and display heart malformations. In addition, Schwann cell precursors and cranial ganglia fail to develop normally. The phenotype demonstrates that in vivo neuregulin acts locally and frequently in a paracrine manner. All cell types affected by the mutation express either erbB3 or erbB4, indicating that either of these tyrosine kinase receptors can be a component in recognition and transmission of essential neuregulin signals.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    et al. Cell 69, 559–572 (1992).

  2. 2.

    et al. Science 256, 1205–1210 (1992).

  3. 3.

    , , , & Cell 72, 801–815 (1993).

  4. 4.

    , et al. Nature 362, 312–318 (1993).

  5. 5.

    & Cell 78, 5–8 (1994).

  6. 6.

    & Bioessays 15, 815–824 (1993).

  7. 7.

    & Acta anat. 130, 264–274 (1987).

  8. 8.

    , , , & Genes Dev. 5, 105–119 (1991).

  9. 9.

    & Proc. natn. Acad. Sci. U.S.A. 91, 1064–1068 (1994).

  10. 10.

    , , , & Neuron 14, 103–115 (1995).

  11. 11.

    , , , & J. biol. Chem. 270, 14523–14532 (1995).

  12. 12.

    , , , & Cell 77, 349–360 (1994).

  13. 13.

    , & Cell Growth Differ. 4, 227–237 (1993).

  14. 14.

    , , , & Proc. natn. Acad. Sci. U.S.A. 92, 1431–1435 (1995).

  15. 15.

    & Am. J. Anat. 166, 445–468 (1983).

  16. 16.

    , & Trends Neurosci. 9, 175–180 (1986).

  17. 17.

    J. exp. Zool. 148, 91–124 (1961).

  18. 18.

    , , , & Nature 337, 461–464 (1989).

  19. 19.

    , & Nature 341, 156–159 (1989).

  20. 20.

    et al. Cell 72, 183–196 (1993).

  21. 21.

    Expl Cell Res. 118, 405–417 (1995).

  22. 22.

    et al. Science 269, 230–234 (1995).

  23. 23.

    & Science 269, 234–238 (1995).

  24. 24.

    et al. Nature 376, 337–341 (1995).

  25. 25.

    , & Nature 336, 348–352 (1988).

  26. 26.

    , & Science 254, 707–710 (1991).

  27. 27.

    in Tetratocarcinomas and Embryonic Stem Cells: A Practical Approach (ed. Robertson, E.) 113–157 (IRL, Oxford, 1987).

  28. 28.

    & in Gene Targeting: A Practical Approach (ed. Joyner, A. L.) 207–215 (IRL, New York, 1993).

  29. 29.

    In Situ Hybridization: A Practical Approach (Oxford Univ. Press, 1992).

  30. 30.

    , , & Proc. natn. Acad. Sci. U.S.A. 92, 6592–6596 (1995).

Download references

Author information

Affiliations

  1. Robert-Roessle-Strasse 10, 13122 Berlin, Germany

    • Dirk Meyer
    •  & Carmen Birchmeier

Authors

  1. Search for Dirk Meyer in:

  2. Search for Carmen Birchmeier in:

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/378386a0

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.